This contract will be to conduct a three-arm, placebo controlled, clinical efficacy study of a standardized extract of hypericum in major depression. The trial is designed specifically to test the reported acute efficacy and safety of hypericum, in DSM-IV major depression in comparison to placebo. A third treatment group, using a selective serotonin re-uptake inhibitor (SSRI), will be included to ensure the validity of the trial. In addition, the design includes a four month follow-up period to monitor longer term effects. It is anticipated that 336 subjects (112 in each arm) will participate in the study and will be enrolled over an 18 month period. Efficacy will be evaluated at 8 weeks (acute efficacy); those responding to treatment will continue for an additional 18 weeks (maintenance). The results of the study will be presented to the advisory Councils of both the Office of Alternative Medicine (OAM) and the NIMH as well as at the annual New Clinical Drug Evaluation Unit (NCDEU) meeting and will be submitted for publication in scientific journals. Details of the study design, including patient entry criteria, randomization procedures and analysis are included in the study protocol. The contractor will be responsible for central coordination of the trial including recruiting clinical sites, finalizing the study design, preparing informed consent documents, providing data forms, training, centralized communication, data entry and management and quality control, as well as statistical analysis, report writing and other related activities. This project will involve a multi center effort and a collaborative relationship with clinical site investigators, and NIMH staff.